Atropisomeric molecules

J. Rebek et al. synthesized novel dibenzoheptalene bislactones via a double intramolecular Cannizzaro reaction for condensation polymerization and remote catalysis studies. These bislactones are chiral, atropisomeric molecules. 

Atropisomerism, the phenomenon of chirality due to restricted rotation about a single bond, has been an intellectually intriguing and practically widely applicable area of stereochemistry from the first resolution of a chiral atrop-isomeric biaryl by Kenner in 1921 through the discovery of numerous naturally occurring atropisomeric molecules and the development of atropisomeric chiral ligands. A high point in the history of atropisomerism must be the central role played by the atropisomeric ligand BINAP in Professor Noyori s share of the Nobel Prize for Chemistry in 2001. 

The word atropisomerism was coined by Kuhn (1) to cover isomerism caused by freezing the internal rotation about a single bond in a molecule. Indeed,... 

The concept of atropisomerism developed to a considerable extent following other developments in chemistry, especially those in spectroscopy. Early work by Kohlrausch (4) and Mizushima (3), based on Raman spectra and dipole moment studies, established that rotational isomers—rotamers—must exist in 1,2-dichloroethane. Pitzer established that there are three energy minima when ethane is rotated about its C—C axis (6). Rotamers about single bonds have been found in a wide variety of organic compounds since then, mainly as a result of the application of vibrational spectroscopy to organic molecules (7). 

Having identified 6 centres of chirality, i.e. 4 due to the side-chains and 2 due to the atropisomerism, a total of 64 optical isomers are possible within each of the rotamers Gl, G2, G3. However, this number is reduced to 16 configurations because of identities which can be visualized as follows The Fischer projections of the iotrolan molecule are split at the bridge into two halves to give the... 

Proceeding from G1 with the E)/ E) conformation to G2 with (Z)/(Z) implies a rotation about bonds b and b as indicated by the bold lines in Fig. 29. As the centres of atropisomerism on each half of the molecule are not affected by this rotation, the projection of the side-chains must be adjusted such that the projections correspond to retainment of the original configuration. The assignment of the peaks is made using the pattern interchange given earlier in Fig. 8. 

Although more work is needed to clearly correlate the type of solubilization site occupied by different porphyrins with their reactivity in such sites towards atropisomerization, it is clear that different sites exist and that these sites show quite different reactivity in both thermal and photochemical processes. Preliminary studies have shown that related behavior probably occurs in other organized assemblies formed by dispersion of surfactant molecules in... 

This reaction proceeds with very high regioselectivity. The other possible regioisomer (coupled at C-7 of the isoquinoline) cannot be detected unless the reaction is performed at higher temperatures (1.2% yield at 130 C). As opposed to the final synthetic target molecules 9/10, which cannot be atropisomerized at higher temperatures, the intermediate lactone exists as helicene-like distorted atropisomers 7 and 8 that interconvert at room temperature with half-lives of less than a minute. 

Consider the case of the first chiral biphenyl to be resolved, one enantiomer of which is shown in 21. To determine the configuration of this enantiomer, one draws a projection formula similar to that previously shown for allenes, but with inclusion of relevant ortho groups this is shown in 22. If one tracks the substituents alphabetically, then the sense of turn between b and c is anti-clockwise, as in 16, and so 22 has S configuration. It is possible to construct molecules that additionally contain substituents at the unsubstituted aromatic carbons of 21 however, any additional substituents are not relevant to the question of atropisomerism. 

The descriptor a stands for axis or axial. Molecules that exhibit atropisomerism are chiral because of the presence of a chiral axis rather than a chirality center. For a discussion of chiral axes and atropisomerism, see E. L. Eliel and S. H. Wilen, Stereochemistry of Organic Compounds, Wiley-Interscience New York, 1994, Chap. 14. 

Full details have now been given of the preparation and characterization of phenylaminophosphines, e.g., (PhNH)3P, from the reaction of dialkylamino-phosphines with aniline, The new atropisomeric chiral diphosphine (72) has been prepared by the reaction of chlorodiphenylphosphine with the appropriate 2,2 -diaminobiphenyl. Related reactions of alcohols and aminoalcohols with chlorodiphenylphosphine have led to several new ligand systems,including the chiral molecules (73) and (74). ... 

Hitosugi S, Nakanishi W, Isobe H (2012) Atropisomerism in a belt-persistent nanohoop molecule rotational restriction forced by macrocyclic ring strain. Chem Asian J 7 1550-2... 

The stereochemical implications of hindered rotation in non-planar molecules, termed atropisomerism, have intrigued chemists since 1921, constituting a challenge in drug discovery. In particular, atropisomerism opens new ways for DKR processes by exploiting the interconversion of atropisomeric unstable... 

---